BACKGROUND & AIMS: Nephropathy affects about one third of diabetic patients and its onset can be predicted almost a decade in advance by detecting small quantities of albumin in the urine (microalbuminuria). Thus, detection of proteinuria or microalbuminuria in diabetic patients carries important implications and merits intervention. Strategies for delaying the relentless progression of microalbuminuria to diabetic nephropathy and ultimately end-stage renal failure are focused on improving glycemic control and reducing blood pressure. Studies with beta-blockers, calcium antagonists, diuretics, and angiotensin-converting enzyme (ACE) inhibitors in hypertensive diabetics with microalbuminuria have shown a significant reduction in urinary albumin excretion rates (AER), with effective lowering of blood pressure. In a crossover study, we compared the effects of captopril versus indapamide as monotherapy for 12 weeks on AER and blood pressure in 31 diabetic patients with established microalbuminuria. The 2 drugs were equally effective in reducing AER (average reduction 30-40%) and had comparable antihypertensive effects.

背景与目标： 肾病影响大约三分之一的糖尿病患者，并且可以通过检测尿液中的少量白蛋白（微量白蛋白尿）提前近十年预测其发病。因此，在糖尿病患者中检测蛋白尿或微量白蛋白尿具有重要意义并值得干预。延迟微量白蛋白尿持续发展至糖尿病性肾病并最终导致终末期肾衰竭的策略集中在改善血糖控制和降低血压上。在具有微量白蛋白尿的高血压糖尿病患者中使用β受体阻滞剂，钙拮抗剂，利尿剂和血管紧张素转换酶（ACE）抑制剂进行的研究表明，尿白蛋白排泄率（AER）显着降低，有效降低了血压。在一项交叉研究中，我们比较了卡托普利和吲达帕胺单药治疗12周对31例已建立微量白蛋白尿的糖尿病患者的AER和血压的影响。这两种药物在降低AER方面同样有效（平均降低30-40％），并且具有可比的降压作用。

BACKGROUND & AIMS: :The possible role of angiotensin-converting enzyme inhibition in preventing or minimizing tolerance to intravenous nitroglycerin in severe congestive heart failure (CHF) was studied by quantitating the degree of tolerance in 12 patients receiving nitroglycerin (group 1) and in 9 patients (group 2) receiving nitroglycerin and concurrent treatment with captopril (60 +/- 29 mg/day). At peak effect, nitroglycerin produced almost identical hemodynamic changes in both groups, with significant decreases in right atrial and pulmonary arterial wedge pressure, systolic blood pressure and systemic and pulmonary vascular resistances. Cardiac index increased. The extent of nitrate tolerance was calculated for each hemodynamic parameter as the percentage loss of the peak effect achieved by the drug. At 24 hours, 98 +/- 80% of the benefit achieved with respect to right atrial pressure was lost in group 1 and 61 +/- 74% in group 2 (group 1 vs 2, difference not significant). For pulmonary arterial wedge pressure, 51 +/- 31% (group 1) and 85 +/- 53% (group 2) (difference not significant) of the effect was lost, and for cardiac index, 53 +/- 58% (group 1) and 54 +/- 44% (group 2) (difference not significant). Tolerance was also almost identical regarding systolic blood pressure and systemic and pulmonary vascular resistance. Thus, the extent of tolerance to high-dose intravenous nitroglycerin in CHF was unaltered by administration of captopril, indicating that in clinical dosage, counter-regulatory neurohumoral mechanisms involving the renin-angiotensin system appear to be unimportant in its development.

背景与目标： ：通过定量分析12名接受硝酸甘油的患者（第1组）和9名患者（第2组）的严重程度，研究了血管紧张素转换酶抑制在预防或最小化严重充血性心力衰竭（CHF）对静脉硝化甘油的耐受性中的可能作用。 ）接受硝酸甘油并同时用卡托普利（60 /-29 mg / day）进行治疗。在达到最佳效果时，两组中的硝酸甘油产生几乎相同的血液动力学变化，右心房和肺动脉楔压，收缩压以及全身和肺血管阻力显着降低。心脏指数增加。针对每个血液动力学参数计算硝酸盐耐受性的程度，作为药物达到的峰值效应的百分比损失。在第24小时，第1组损失了98 /-80％的右心房压力获益，第2组损失了61 /-74％（第1组vs 2，差异不显着）。对于肺动脉楔压，失去了51 /-31％（第1组）和85 /-53％（第2组）（效果不显着），而对于心脏指数，则为53 /-58％（第1组）和54 /-44％（第2组）（差异不明显）。在收缩压以及全身和肺血管阻力方面，耐受性也几乎相同。因此，卡托普利的使用不会改变CHF对大剂量静脉内硝酸甘油的耐受程度，这表明在临床剂量中，涉及肾素-血管紧张素系统的反调节神经体液机制在其发展中似乎并不重要。

BACKGROUND & AIMS: :The myocardial protective effect of captopril cardioplegia was investigated through the recovery of cardiac functions, biochemical changes and ultrastructural assays in the isolated working rabbit heart after hypothermic ischemic arrest for 3 hours. Hearts were randomly divided into 3 groups with 8 in each. Another 3 groups of hearts (8 in each) were arranged for studying the biochemical changes and ultrastructure during the ischemic period. In the control group (I), the hearts were protected by the modified St. Thomas' cardioplegic solution No. I, while in Group II and III the cardioplegic solutions contained 2.3 mumol/L and 23 mumol/L captopril respectively. The results showed that the percent recoveries of cardiac function in the 23 mumol/L captopril group compared with the control group were 97.9 +/- 9.8% vs 84.9 +/- 7.3% in left ventricular peak systolic pressure (P less than 0.01), 118 +/- 33% vs 79 +/- 20% in +dp/dt max (P less than 0.01), 111 +/- 22% vs 75 +/- 18% in -dp/dt max (P less than 0.01), 145.6 +/- 44.8% vs 76.7 +/- 18% in coronary flow (P less than 0.01), 120.2 +/- 45.7% vs 36.4 +/- 22.2% in aortic flow (P less than 0.01), 127.4 +/- 27.3% vs 56.1 +/- 14% in cardiac output (P less than 0.01), and 118.2 +/- 33.5% vs 52.5 +/- 19.9% in stroke volume (P less than 0.01) respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

背景与目标： 卡托普利心脏停搏的心肌保护作用是通过低温缺血性停搏3小时后分离的工作兔心脏的心脏功能恢复，生化变化和超微结构分析来研究的。将心脏随机分为3组，每组8个。安排另外3组心脏（每组8个）用于研究缺血期的生化变化和超微结构。在对照组（I）中，心脏受到改良的I型圣托马斯心脏停搏液的保护，而在第二组和第三组中，心脏停搏液分别含有2.3摩尔/升和23摩尔/升的卡托普利。结果显示，卡托普利组23摩尔/升与对照组相比，心功能恢复百分率分别为97.9 /-9.8％和84.9 /-7.3％（P小于0.01），118 / -dp / dt max的33％vs 79 /-20％（P小于0.01），111 /-22％vs-dp / dt max的75％-18％（P小于0.01），145.6 /-44.8％ vs冠脉血流76.7 /-18％（P小于0.01），主动脉血流120.2 /-45.7％vs 36.4 /-22.2％（心脏小于P）0.01、127.4 /-27.3％vs 56.1 /-14％输出（P小于0.01）和118.2 /-33.5％对52.5 /-19.9％的笔触量（P小于0.01）（摘要截断为250个字）

BACKGROUND & AIMS: :The aim of the study was to evaluate whether the combination of ketanserin with captopril exerts an additive antihypertensive effect, as compared with single drug treatment. Twelve patients with uncomplicated moderate essential hypertension received, according to a randomized, double-blind, crossover design, ketanserin (40 mg twice daily), captopril (50 mg twice daily), the combination of the two drugs at these dosages, and the corresponding placebo, each treatment being given for 1 month. Both ketanserin and captopril as monotherapy similarly and significantly reduced blood pressure as compared with placebo (p less than 0.001). The combination treatment of ketanserin plus captopril further and significantly reduced blood pressure when compared with single drug treatment (p less than 0.001). Moreover, the percentage of responders and patients whose blood pressure was normalized were significantly greater under the combined treatment than under ketanserin or captopril monotherapy (p less than 0.001). These data indicate that the combination of ketanserin plus captopril exerts a clear additive antihypertensive effect when compared with each treatment as monotherapy, a finding that suggests this combination can be usefully employed in the treatment of hypertensive patients.

背景与目标： ：该研究的目的是评估与单药治疗相比，酮色林与卡托普利的组合是否具有附加的降压作用。根据随机，双盲，交叉设计，对十二例无并发症中度原发性高血压的患者接受了酮色林（40 mg每天两次），卡托普利（50 mg每天两次），这两种剂量的两种药物的组合以及相应的治疗安慰剂，每次治疗1个月。与安慰剂相比，酮色林和卡托普利的单药治疗相似且显着降低了血压（p小于0.001）。与单药治疗相比，酮色林加卡托普利的联合治疗可进一步显着降低血压（p小于0.001）。此外，与酮色林或卡托普利单药治疗相比，联合治疗下应答者和血压正常化患者的百分比显着更高（p小于0.001）。这些数据表明，与作为单一疗法的每种疗法相比，酮色林加卡托普利的组合具有明显的加性降压作用，这一发现表明该组合可以有效地用于治疗高血压患者。

BACKGROUND & AIMS: :Polyamines are thought to play an essential role in cellular hypertrophy and proliferation. Ornithine decarboxylase (ODC) catalyzes the first and probably the rate-limiting step in biosynthesis of polyamines. In this study, we evaluated the pathophysiological role of the renin-angiotensin system in isoproterenol-induced cardiac hypertrophy, using myocardial ODC activity as an indicator of cardiac hypertrophy. Isoproterenol caused an eight-fold increase of myocardial ODC activity in normotensive Wistar rats within 4 h after injection. Captopril suppressed the induction of ODC by isoproterenol to two-thirds of the control level. These results indicate that the renin-angiotensin system may participate in the induction of myocardial hypertrophy by isoproterenol.

背景与目标： ：多胺被认为在细胞肥大和增殖中起重要作用。鸟氨酸脱羧酶（ODC）催化生物合成多胺的第一步，也可能是限速步骤。在这项研究中，我们使用心肌ODC活性作为心肌肥大的指标，评估了肾素-血管紧张素系统在异丙肾上腺素诱发的心肌肥大中的病理生理作用。注射后4小时内，异丙肾上腺素使血压正常的Wistar大鼠心肌ODC活性增加了八倍。卡托普利将异丙肾上腺素对ODC的诱导抑制到对照水平的三分之二。这些结果表明，肾素-血管紧张素系统可能参与了异丙肾上腺素对心肌肥大的诱导。

BACKGROUND & AIMS: :This study was conducted to examine the role of bradykinin in the persistence of the renal vasodilator effect of captopril during angiotensin II receptor blockade. Blood pressure and renal blood flow were monitored in eight groups of pentobarbital-anesthetized rabbits. In group 4, captopril alone was administered, and it decreased blood pressure by 14 +/- 4 mm Hg and increased renal blood flow by 21 +/- 4 ml/min. After a bolus injection and a constant intravenous infusion of the imidazole derivative angiotensin II receptor antagonist DuP 753 (group 5), captopril decreased blood pressure by 9 +/- 2 mm Hg and increased renal blood flow by 8 +/- 1 ml/min (12 +/- 1% change in renal blood flow, p less than 0.05 versus group 4). In the presence of a constant intravenous infusion of saralasin (group 6), captopril decreased blood pressure by 13 +/- 5 mm Hg and increased renal blood flow by 7 +/- 2 ml/min (17 +/- 5% change in renal blood flow, p less than 0.05 versus group 4). These results did not differ from those in group 5. During a constant intrarenal arterial infusion of a B2 bradykinin receptor antagonist, DArg0, [Hyp3-Thi5,8-DPhe7]-bradykinin (BkA) (group 7), captopril decreased blood pressure by 14 +/- 4 mm Hg and increased renal blood flow by 10 +/- 4 ml/min. Combined administration of DuP 753 intravenously and BkA intra-arterially (group 8) eliminated the effect of captopril. In group 8, captopril caused insignificant changes in blood pressure and renal blood flow. The results indicate that DuP 753 and saralasin antagonize the renin-angiotensin system to a comparable extent in vivo. Although blockade of the latter system accounted for a significant part of the increase in renal blood flow caused by captopril, the remaining component was contributed by endogenous bradykinin.

背景与目标： ：本研究旨在检查缓激肽在血管紧张素II受体阻断期间卡托普利对肾脏血管舒张作用的持续作用中的作用。在八组戊巴比妥麻醉的兔子中监测血压和肾血流量。在第4组中，单独使用卡托普利，它使血压降低了14 4 mm Hg，并使肾血流量增加了21 4 ml / min。推注并持续静脉注射咪唑衍生物血管紧张素II受体拮抗剂DuP 753（第5组）后，卡托普利可使血压降低9 /-2 mm Hg，并使肾血流量增加8 /-1 ml / min（12 /-肾血流量变化1％，与第4组相比，p小于0.05。在持续不断地静脉注射撒拉辛（第6组）的情况下，卡托普利可使血压降低13 /-5 mm Hg，并使肾血流量增加7 /-2 ml / min（肾血流量变化17 /-5％） ，与第4组相比，p小于0.05）。这些结果与第5组没有差异。在恒定的肾动脉内输注B2缓激肽受体拮抗剂DArg0，[Hyp3-Thi5,8-DPhe7]-缓激肽（BkA）（第7组）期间，卡托普利可通过14 /-4 mm Hg和增加10 /-4 ml / min的肾血流量。静脉内联合DuP 753和动脉内BkA联合给药（第8组）消除了卡托普利的作用。在第8组中，卡托普利引起的血压和肾脏血流变化不明显。结果表明，DuP 753和aralasin在体内具有相当程度的拮抗肾素-血管紧张素系统的作用。尽管后一种系统的阻断在卡托普利引起的肾血流量增加中占了很大一部分，但其余成分是由内源性缓激肽引起的。

BACKGROUND & AIMS: The effects of captopril, an angiotensin-converting enzyme inhibitor (ACEI), and a selective B2 kinin receptor antagonist (Icatibant) were examined on the paw edema and tissue contents of bradykinin (BK) and des[Arg9]BK following the intraplantar injection of carrageenan in rats. To this end, BK-like immunoreactivity (BK-LI) and des[Arg9]BK-LI were measured with highly sensitive and specific chemiluminescent enzyme immunoassays. Because pentobarbital significantly reduced the carrageenan-induced edema between 3 and 8 h, experiments were conducted in conscious rats. Icatibant (32.5 nmol/paw; intraplantar) significantly reduced carrageenan-induced paw edema between 3 and 8 h in captopril-untreated rats and at 1 and 3 h in captopril-treated rats (0.2 mg/kg x 5 days, per os). The paw content of BK-LI was increased 10-fold in captopril-untreated and 29-fold in captopril-treated rats 1 h after carrageenan injection. In parallel, des[Arg9]BK-LI was increased 8-fold in captopril-untreated and 24-fold in captopril-treated rats. Icatibant prevented the maximal increases in BK-LI and des[Arg9]BK-LI induced by carrageenan. It is concluded that inhibition of ACE by captopril enhanced the early production of endogenous BK and the edema formation induced by carrageenan through a B2 receptor-mediated mechanism. However, the B2 receptor does not appear to be involved in the late phase of the inflammatory response (from 5 to 24 h) to carrageenan in rats pretreated with ACEI. Although the concentrations of des[Arg9]BK were greater than those of BK, it is unlikely that B1 receptors play a significant role in this model of carrageenan-induced edema.

背景与目标： 足底注射异丙酚后，检查了卡托普利，血管紧张素转换酶抑制剂（ACEI）和选择性B2激肽受体拮抗剂（Icatibant）对爪水肿和缓激肽（BK）和des [Arg9] BK的组织含量的影响。大鼠中的角叉菜胶。为此，用高灵敏度和特异性的化学发光酶免疫测定法测量了BK样免疫反应性（BK-LI）和des [Arg9] BK-LI。由于戊巴比妥可在3至8小时内显着减少角叉菜胶引起的水肿，因此在有意识的大鼠中进行了实验。伊卡替班（32.5 nmol /爪；足底内）在未经卡托普利治疗的大鼠中3至8小时以及经卡托普利治疗的大鼠1至3小时内均显着减少了角叉菜胶诱导的爪水肿（0.2 mg / kg x 5天，每次口服）。角叉菜胶注射后1小时，未经卡托普利治疗的大鼠的BK-LI的爪子含量增加10倍，而经卡托普利治疗的大鼠的BK-LI的爪子含量增加29倍。平行地，在未经卡托普利治疗的大鼠中，des [Arg9] BK-LI增加了8倍，而在经卡托普利治疗的大鼠中，des [Arg9] BK-LI增加了24倍。伊卡替班预防了由角叉菜胶诱导的BK-LI和des [Arg9] BK-LI的最大增加。结论是，卡托普利对ACE的抑制作用通过B2受体介导的机制增强了内源性BK的早期产生和角叉菜胶诱导的水肿形成。但是，在用ACEI预处理的大鼠中，B2受体似乎不参与对角叉菜胶的炎症反应的后期（5至24小时）。尽管des [Arg9] BK的浓度高于BK的浓度，但B1受体不太可能在这种由角叉菜胶诱发的水肿模型中发挥重要作用。

BACKGROUND & AIMS: :We treated 94 patients by percutaneous transluminal angioplasty (PTA) for renal artery stenosis (RAS). Prior to PTA, a renogram during angiotensin converting enzyme (ACE) inhibition with captopril was performed, but the result did not influence the decision to treat. The parenchymal time activity curves were judged by visual interpretation. Of the 94 patients, 51 had unilateral and 43 bilateral RAS. In 17 patients with bilateral RAS, PTA could be performed only in the least affected kidney; because of this the effect of PTA on their blood pressure could not be evaluated. Of the remaining 77 patients, a positive captopril renogram was seen in all 31 cured patients, in 22 of the 27 patients with improvement, and in six of the 19 patients with no change of their blood pressure. The sensitivity of the tests for cure and improvement of the blood pressure was 91% (53/58 patients) for all patients, 95% in patients with unilateral RAS (35/37), and 86% (18/21 patients) in patients with bilateral RAS, bilaterally treated. In 18 patients with a negative captopril renogram the blood pressure improved in five, and did not change in 13 patients. The success of PTA in patients with a negative captopril renogram was so poor that we feel it would have been better not to have performed angiography and PTA at all. In conclusion, captopril renography is a useful investigation in assessing the likelihood of blood pressure reduction after PTA of renal artery stenosis.

背景与目标： ：我们通过经皮腔内血管成形术（PTA）治疗了94例肾动脉狭窄（RAS）患者。在进行PTA之前，在用卡托普利抑制血管紧张素转化酶（ACE）的过程中进行了肾图检查，但结果并未影响治疗决定。实质时间活动曲线通过视觉解释来判断。在94例患者中，有51例为单侧RAS，有43例为双侧RAS。在17例双侧RAS患者中，仅可在受影响最小的肾脏中进行PTA。因此，无法评估PTA对他们的血压的影响。在其余的77例患者中，所有31例治愈的患者，27例好转的患者中有22例，血压没有变化的19例中的6例均显示卡托普利肾图检查阳性。所有患者对治愈和改善血压的测试的敏感性分别为91％（53/58患者），单侧RAS患者（95/35）和95％（18/21患者）双侧RAS，双侧治疗。卡托普利肾电图阴性的18例患者中，有5例血压有所改善，而13例患者中血压没有变化。卡托普利肾电图阴性的患者中PTA的成功非常差，以至于完全不进行血管造影和PTA会更好。总之，卡托普利肾造影是一项有用的研究，可用于评估PTA肾动脉狭窄后血压降低的可能性。

BACKGROUND & AIMS: BACKGROUND:The ELITE study showed an association between the angiotensin II antagonist losartan and an unexpected survival benefit in elderly heart-failure patients, compared with captopril, an angiotensin-converting-enzyme (ACE) inhibitor. We did the ELITE II Losartan Heart Failure Survival Study to confirm whether losartan is superior to captopril in improving survival and is better tolerated. METHODS:We undertook a double-blind, randomised, controlled trial of 3,152 patients aged 60 years or older with New York Heart Association class II-IV heart failure and ejection fraction of 40% or less. Patients, stratified for beta-blocker use, were randomly assigned losartan (n=1,578) titrated to 50 mg once daily or captopril (n=1,574) titrated to 50 mg three times daily. The primary and secondary endpoints were all-cause mortality, and sudden death or resuscitated arrest. We assessed safety and tolerability. Analysis was by intention to treat. FINDINGS:Median follow-up was 555 days. There were no significant differences in all-cause mortality (11.7 vs 10.4% average annual mortality rate) or sudden death or resuscitated arrests (9.0 vs 7.3%) between the two treatment groups (hazard ratios 1.13 [95.7% CI 0.95-1.35], p=0.16 and 1.25 [95% CI 0.98-1.60], p=0.08). Significantly fewer patients in the losartan group (excluding those who died) discontinued study treatment because of adverse effects (9.7 vs 14.7%, p<0.001), including cough (0.3 vs 2.7%).

背景与目标： 背景：ELITE研究表明，与血管紧张素转换酶（ACE）抑制剂卡托普利相比，血管紧张素II拮抗剂洛沙坦与老年心衰患者的意外生存获益之间存在关联。我们进行了ELITE II Losartan心力衰竭生存研究，以确认氯沙坦在改善生存率和耐受性方面是否优于卡托普利。
方法：我们进行了一项双盲，随机，对照试验，研究对象为3,152名60岁以上的纽约心脏协会II-IV级心力衰竭且射血分数小于或等于40％的患者。随机分组接受β-受体阻滞剂治疗的患者，每天随机分配一次洛沙坦（n = 1,578）滴定至50 mg或每天3次将卡托普利（n = 1,574）滴定至50 mg。主要终点和次要终点是全因死亡率，突然死亡或复苏的逮捕。我们评估了安全性和耐受性。分析是按意向进行的。
结果：中位随访时间为555天。两个治疗组之间的全因死亡率（年平均死亡率分别为11.7和10.4％）或突然死亡或复苏的逮捕（9.0和7.3％）没有显着差异（危险比1.13 [95.7％CI 0.95-1.35]， p = 0.16和1.25 [95％CI 0.98-1.60]，p = 0.08）。氯沙坦组中，因不良反应（9.7 vs 14.7％，p <0.001），包括咳嗽（0.3 vs 2.7％）而中止研究治疗的患者显着减少（不包括死亡的患者）。

BACKGROUND & AIMS: :Lipid peroxides and fluorescent serum proteins, possible markers of free radical activity, are increased in diabetic patients, particularly those with angiopathy. Captopril, an angiotensin converting enzyme (ACE) inhibitor, scavenges free radicals in vitro independently of ACE inhibition. This is probably due to the presence of a sulphydryl group which is not present in other ACE inhibitor drugs. We have compared the effects of captopril and enalapril on free radical activity in thirty-two diabetic subjects with hypertension (BP greater than 160/95 mmHg). After a three week run-in period on no antihypertensive therapy, patients were randomly allocated to receive captopril or enalapril, the dose titrated according to BP response. After three months, BP was well controlled in both groups and glycaemic control unchanged. Both drugs were associated with a reduction of fluorescent IgG (captopril:Baseline [BL] 0.564 vs. 12 weeks [w] 0.428, P less than 0.05, enalapril:BL 0.603 vs. 12w 0.422 P less than 0.05) and thiobarbituric acid reactive material (captopril:BL 2.35 nmol MDA vs. 12w 1.46 nmol, P less than 0.05, enalapril:BL 2.44 nmol vs. 12w 1.72 nmol, P less than 0.01). In contrast to in vitro studies, there was no significant difference between the drugs when used in therapeutic doses, questioning a hypothesised advantage of captopril over enalapril.

背景与目标： ：脂质过氧化物和荧光血清蛋白，可能是自由基活性的标志物，在糖尿病患者，特别是患有血管病的患者中增加。卡托普利是一种血管紧张素转化酶（ACE）抑制剂，可在体外独立于ACE抑制清除自由基。这可能是由于存在其他ACE抑制剂药物中不存在的巯基。我们比较了卡托普利和依那普利对32例糖尿病高血压患者的自由基活性的影响（血压大于160/95 mmHg）。经过三周的无高血压治疗磨合期后，患者被随机分配接受卡托普利或依那普利治疗，剂量根据BP反应而调整。三个月后，两组血压均得到良好控制，血糖控制未改变。两种药物均与荧光IgG（卡托普利：基线[BL] 0.564比12周[w] 0.428，P小于0.05，依那普利：BL 0.603与12w 0.422 P小于0.05）的降低和硫代巴比妥酸反应性物质有关。 （卡托普利：BL 2.35 nmol MDA相对于12w 1.46 nmol，P小于0.05，依那普利：BL 2.44 nmol对12w 1.72 nmol，P小于0.01）。与体外研究相反，当以治疗剂量使用时，两种药物之间没有显着差异，这质疑了卡托普利相对于依那普利的假设优势。

BACKGROUND & AIMS: :The purpose of current study was to examine the possible involvement of captopril, an angiotensin-converting enzyme inhibitor, on nociception, morphine analgesia and morphine tolerance development involving inflammation and ER-stress pathways in rats. In this study, thirty-six male Wistar rats were used. Animals were divided into six groups: Saline, 50 mg/kg captopril, 5 mg/kg morphine, morphine + captopril, morphine tolerance and morphine tolerance + captopril. The resulting analgesic effect was measured with hot plate and tail flick analgesia tests. The dorsal root ganglions (DRG) tissues were collected for inflammation parameters, endoplasmic reticulum (ER) stress and apoptosis proteins by using ELISA. Captopril showed anti-nociceptive effect when given alone (p < 0.05 to p < 0.01). In addition, captopril increased the analgesic effect of morphine (p < 0.05 to p < 0.001) and also decreased the tolerance to morphine at a significant level (p < 0.05 to p < 0.001). However, it decreased inflammation and ER-stress when applied with single-dose morphine and tolerance induction (p < 0.001). Moreover, captopril decreased apoptosis proteins after tolerance development (p < 0.001). In conclusion, captopril has antinociceptive properties, increasing analgesic effect of morphine, and preventing tolerance development. These effects may occur by suppressing inflammation and ER-stress pathways.

背景与目标： ：本研究的目的是研究血管紧张素转化酶抑制剂卡托普利对涉及炎症和内质网应激通路的伤害感受，吗啡镇痛和吗啡耐受性发展的可能影响。在这项研究中，使用了三十六只雄性Wistar大鼠。将动物分为六组：盐水，50mg / kg卡托普利，5mg / kg吗啡，吗啡卡托普利，吗啡耐受性和吗啡耐受性卡托普利。通过热板和甩尾镇痛测试来测量所产生的镇痛效果。使用ELISA收集背根神经节（DRG）组织的炎症参数，内质网（ER）应激和凋亡蛋白。卡托普利单独使用时显示抗伤害作用（p <0.05至p <0.01）。此外，卡托普利提高了吗啡的镇痛作用（p <0.05至p <0.001），并且在一定水平上也降低了对吗啡的耐受性（p <0.05至p <0.001）。但是，与单剂量吗啡和耐受性诱导剂一起使用时，它可以减少炎症和内质网应激（p <0.001）。此外，卡托普利在耐受性发展后降低凋亡蛋白（p <0.001）。总之，卡托普利具有镇痛作用，可增强吗啡的止痛作用，并防止耐受性的发展。这些作用可能是通过抑制炎症和内质网应激途径而发生的。

BACKGROUND & AIMS: Congestive heart failure (CHF) is a syndrome characterized by increased levels of angiotensin II (Ang II) and endothelin-1 (ET-1). In vitro, Ang II stimulates ET-1 release. The purpose of the study was to assess the effect of a single dose of an angiotensin-converting enzyme inhibitor (ACEI) captopril versus placebo on plasma endothelin concentration in human congestive heart failure. Captopril (25 mg, given orally) was compared with placebo in a group of 20 patients with systolic dysfunction in a double-blind randomized study. Plasma irET concentration was significantly increased in CHF patients compared with normal subjects (5.59 pg/ml +/- 0.35 vs. 3.58 pg/ml +/- 0.99, p < 0.0002). Despite the decrease in systolic blood pressure and the increase in plasma renin activity, suggesting a significant blockade of the renin-angiotensin system, no difference in plasma irET-1 was observed between captopril and placebo. Our results suggest that captopril does not acutely influence irET-1 plasma concentration in human CHF. These data do not support the hypothesis that the acute vasodilator effect of a single dose of 25 mg of captopril given daily orally involves modulation of the increased plasma concentration of endothelin observed in CHF.

背景与目标： 充血性心力衰竭（CHF）是一种以血管紧张素II（Ang II）和内皮素1（ET-1）水平升高为特征的综合征。在体外，Ang II刺激ET-1释放。该研究的目的是评估单剂量血管紧张素转换酶抑制剂（ACEI）卡托普利与安慰剂对人充血性心力衰竭血浆内皮素浓度的影响。在一项双盲随机研究中，将卡托普利（25毫克，口服）与20例收缩期功能障碍的患者的安慰剂进行了比较。与正常受试者相比，CHF患者的血浆irET浓度显着增加（5.59 pg / ml /-0.35和3.58 pg / ml /-0.99，p <0.0002）。尽管收缩压降低和血浆肾素活性增加，提示肾素-血管紧张素系统被显着阻断，但卡托普利和安慰剂之间的血浆irET-1没有差异。我们的结果表明，卡托普利不会严重影响人CHF中的irET-1血浆浓度。这些数据不支持这样的假说，即每天口服25 mg卡托普利的单次剂量的急性血管扩张作用涉及调节CHF中所观察到的内皮素血浆浓度的升高。

BACKGROUND & AIMS: :Three groups of New Zealand white rabbits were used to study the effects of captopril on the renin-angiotensin system and sympathetic nervous system during sodium nitroprusside (SNP)-induced hypotension and halothane anesthesia. Two groups of rabbits (C and CH) were treated with captopril 2 mg/kg i.v. One captopril-treated group (CH) and the third, untreated group (H) received SNP to induce hypotension. In these two groups, the mean arterial blood pressure (MAP) was reduced by 40% for 150 min. Group C did not undergo SNP-induced hypotension and served to document the effects of captopril alone during the 150-min study period. Arterial blood samples for norepinephrine (NE), epinephrine (EPI), and plasma renin activity (PRA) were drawn prior to, during hypotension, and in the recovery period. The SNP dose required to maintain the hypotension was continuously recorded. NE, EPI, and PRA all increased in group H, indicating activation of both the renin-angiotensin system and the sympathetic system during hypotension. This was accompanied by a dramatic increase in SNP dose requirement. In the CH group, PRA levels rose sharply and remained elevated. Plasma NE levels increased, while EPI levels remained unchanged with a decline in the SNP dose requirement. The C group demonstrated a rise in PRA levels, accompanied by unchanged NE and EPI levels and MAP during the study period. Captopril administration decreased the SNP dose requirement and significantly decreased the sympathetic response (measured by NE and EPI levels) in group CH as compared to the H group.(ABSTRACT TRUNCATED AT 250 WORDS)

背景与目标： ：三组新西兰白兔用于研究卡托普利对硝普钠（SNP）引起的低血压和氟烷麻醉下肾素-血管紧张素系统和交感神经系统的影响。两组兔子（C和CH）分别经卡托普利2 mg / kg静脉内治疗。一个卡托普利治疗组（CH）和第三个未经治疗组（H）接受SNP诱导低血压。在这两组中，平均动脉压（MAP）在150分钟内降低了40％。 C组未经历SNP引起的低血压，并在150分钟的研究期内用于证明卡托普利的作用。在降压之前，降压期间和恢复期间抽取了去甲肾上腺素（NE），肾上腺素（EPI）和血浆肾素活性（PRA）的动脉血样品。持续记录维持低血压所需的SNP剂量。 H组的NE，EPI和PRA均升高，表明低血压期间肾素-血管紧张素系统和交感神经系统均被激活。这伴随着SNP剂量需求的急剧增加。在CH组，PRA水平急剧上升并保持较高水平。血浆NE水平增加，而EPI水平保持不变，但SNP剂量要求却下降了。在研究期间，C组表现出PRA水平升高，同时NE和EPI水平和MAP保持不变。与H组相比，卡托普利给药降低了CH组的SNP剂量需求并显着降低了交感反应（通过NE和EPI水平测量）（摘要截断为250字）

BACKGROUND & AIMS: :To study the hemodynamic and neurohumoral effects of hydralazine versus captopril after the first dose, 15 patients with idiopathic dilated cardiomyopathy (NYHA Class II and III) were included in a crossover trial with a washout period of three days. Hemodynamic parameters were measured by using a Swan-Ganz thermodilution catheter, and venous blood was sampled during supine rest and standardized upright exercise before (control) and 60 min after drug administration. Compared to the control phase, hydralazine induced an increase in heart rate and cardiac index (p less than 0.01), and a decrease in mean arterial pressure and pulmonary wedge pressure (p less than 0.01, p less than 0.05, respectively). The hemodynamic effects were associated with increased norepinephrine plasma concentration during upright exercise (p less than 0.05) and increased plasma renin activity (p less than 0.01). After administration of captopril, heart rate at rest (p less than 0.05), mean arterial pressure, and pulmonary wedge pressure decreased significantly (p less than 0.01). Cardiac index remained unchanged. Norepinephrine plasma concentrations were not significantly influenced despite a tendency to lower levels during upright exercise. Plasma renin activity increased (p less than 0.01) and aldosterone at rest decreased significantly (p less than 0.05). These differences in neurohumoral response between both drugs may be important for their long-term effects.

背景与目标： ：为研究肼苯哒嗪和卡托普利在首次给药后的血流动力学和神经体液作用，在一项交叉试验中纳入了15名特发性扩张型心肌病（NYHA II级和III级）患者，洗脱期为3天。通过使用Swan-Ganz热稀释导管测量血流动力学参数，并在给药前（对照）和给药后60分钟，在仰卧休息和标准化直立运动期间对静脉血进行采样。与对照期相比，肼苯哒嗪引起心率和心脏指数增加（p小于0.01），平均动脉压和肺楔压降低（p分别小于0.01和p小于0.05）。血液动力学效应与在直立运动期间增加去甲肾上腺素的血浆浓度（p小于0.05）和增加血浆肾素活性（p小于0.01）有关。服用卡托普利后，静息心率（p小于0.05），平均动脉压和肺楔压显着降低（p小于0.01）。心脏指数保持不变。尽管在直立运动过程中去甲肾上腺素的血浆浓度有降低的趋势，但并未显着影响血浆中的浓度。血浆肾素活性增加（p小于0.01），静止时醛固酮明显降低（p小于0.05）。两种药物之间神经体液反应的这些差异可能对它们的长期作用很重要。